Yang Feng-Ying, Xu Lyu-Hong, Wang Jian, Zhang Ya-Ting, Lin Shao-Fen, Wang Kai-Mei, Zhou Dun-Hua, Fang Jian-Pei
Department of Pediatrics, SUN Yat-Sen Memorial Hospital, SUN Yat-Sen University, Guangzhou 510120, Guangdong Province, China,Department of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou 510000, Guangdong Province, China.
Department of Pediatrics, SUN Yat-Sen Memorial Hospital, SUN Yat-Sen University, Guangzhou 510120, Guangdong Province, China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023;31(4):967-972. doi: 10.19746/j.cnki.issn.1009-2137.2023.04.006.
To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL).
A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed.
Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with C677T mutations (CT+TT genotypes) had a higher risk of leukopenia (=2.38), neutropenia (=2.2), anemia (=1.83) and hepatoxicity (=1.98). However, no significant difference was found in the MTX plasma concentration between the C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX.
The C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.
探讨亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性对急性淋巴细胞白血病（ALL）患儿大剂量甲氨蝶呤（MTX）不良反应的影响。
选取2018年11月至2020年10月在中山大学孙逸仙纪念医院儿科住院的69例ALL患儿纳入本研究。收集患儿临床资料，采集外周血分离白细胞，采用数字荧光分子杂交技术进行基因分型。化疗期间监测MTX的不良反应及血浆药物浓度，并分析基因多态性对MTX不良反应及血浆药物浓度的影响。
在中高危患儿中，与野生型组（CC基因型）相比，C677T突变型（CT+TT基因型）患儿发生白细胞减少（=2.38）、中性粒细胞减少（=2.2）、贫血（=1.83）及肝毒性（=1.98）的风险更高。然而，C677T突变组与野生型组在不同时间点（24 h、48 h和72 h）的MTX血浆浓度无显著差异。多因素分析显示，MTX血浆浓度（48 h）、ALL临床危险度及C677T基因多态性是大剂量MTX不良反应的独立影响因素。
C677T突变可能与ALL患儿大剂量MTX治疗后的骨髓抑制及肝毒性有关。
